Intraoperative adverse events among surgeons in Singapore: a multicentre cross-sectional study on impact and support.

BACKGROUND: It is known that many surgeons encounter intraoperative adverse events which can result in Second Victim Syndrome (SVS), with significant detriment to their emotional and physical health. There is, however, a paucity of Asian studies in this space. The present study thus aimed to explore the degree to which the experience of an adverse event is common among surgeons in Singapore, as well as its impact, and factors affecting their responses and perceived support systems. METHODS: A self-administered survey was sent to surgeons at four large tertiary hospitals. The 42-item questionnaire used a systematic closed and open approach, to assess: Personal experience with intraoperative adverse events, emotional, psychological and physical impact of these events and perceived support systems. RESULTS: The response rate was 57.5% (n = 196). Most respondents were male (54.8%), between 35 and 44 years old, and holding the senior consultant position. In the past 12 months alone, 68.9% recalled an adverse event. The emotional impact was significant, including sadness (63.1%), guilt (53.1%) and anxiety (45.4%). Speaking to colleagues was the most helpful support source (66.7%) and almost all surgeons did not receive counselling (93.3%), with the majority deeming it unnecessary (72.2%). Notably, 68.1% of the surgeons had positive takeaways, gaining new insight and improving vigilance towards errors. Both gender and surgeon experience did not affect the likelihood of errors and emotional impact, but more experienced surgeons were less likely to have positive takeaways (p = 0.035). Individuals may become advocates for patient safety, while simultaneously championing the cause of psychological support for others. CONCLUSIONS: Intraoperative adverse events are prevalent and its emotional impact is significant, regardless of the surgeon's experience or gender. While colleagues and peer discussions are a pillar of support, healthcare institutions should do more to address the impact and ensuing consequences.

Risk of Parkinson's disease in hepatitis B and C populations: a systematic review and meta-analysis.

Parkinson's disease (PD) is a common neurodegenerative disorder, and its association with viral hepatitis has been debated. We performed a meta-analysis to examine the association between PD risk and viral hepatitis. Medline, EMBASE, and the Cochrane library were searched from inception till July 2022. Meta-analysis was conducted using a fixed-effect model with the inverse variance method. Three groups were compared to controls: infection with either hepatitis B or C virus (HBV and HCV, respectively), or coinfection with both viruses. We found 551 records, and six studies comprising of 2,566,947 patients were included in the analysis. PD risk was increased in HCV-infected population (OR 1.10, 95% CI 1.03-1.17, p = 0.005) and (HR 1.37, 95% CI 1.26-1.49, p < 0.001). This increase was not observed for the HBV-infected and HBV-HCV-coinfected coinfection populations. For pooled OR, the risk was significantly lower in HBV-infected (OR 0.79, 95% CI 0.76-0.83, p < 0.001) but not significantly different in HBV-HCV-coinfected populations (OR 0.96, 95% CI 0.82-1.12, p = 0.57). For pooled HR, the risk was significantly higher in both HBV-infected (HR 1.22, 95% CI 1.14-1.31, p < 0.001) and HBV-HCV-coinfected populations (HR 1.29, 95% CI 1.05-1.58, p = 0.013). We found that the risk of PD was increased in the HCV-infected population, but results were inconsistent in those with HBV and HBV-HCV infections. Our findings provide impetus for further clinical and functional studies to unravel the role of the adaptive immune system in PD.

Testicular self-examination for early detection of testicular cancer.

Testicular cancer (TCa) commonly presents as a painless scrotal mass. It has been suggested that testicular self-examination (TSE) can help in early detection and thus potentially improve treatment outcomes and prognosis. While TSE is more well established in guideline recommendations for patients with a known history of TCa, its role in healthy young men is less established and controversial. In this paper, we review contemporary data to provide an updated recommendation.

Should Procalcitonin Be Included in Acute Cholecystitis Guidelines? A Systematic Review.

Background and Objectives: Acute cholecystitis (AC) is a common surgical emergency. Recent evidence suggests that serum procalcitonin (PCT) is superior to leukocytosis and serum C-reactive protein in the diagnosis and severity stratification of acute infections. This review evaluates the role of PCT in AC diagnosis, severity stratification, and management. Materials and Methods: PubMed, Embase, and Scopus were searched from inception till 21 August 2022 for studies reporting the role of PCT in AC. A qualitative analysis of the existing literature was conducted. Results: Five articles, including 688 patients, were included. PCT ≤ 0.52 ng/mL had fair discriminative ability (Area under the curve (AUC) 0.721, p < 0.001) to differentiate Grade 1 from Grade 2-3 AC, and PCT > 0.8 ng/mL had good discriminatory ability to differentiate Grade 3 from 1-2 AC (AUC 0.813, p < 0.001). PCT cut-off ≥ 1.50 ng/mL predicted difficult laparoscopic cholecystectomy (sensitivity 91.3%, specificity 76.8%). The incidence of open conversion was higher with PCT ≥ 1 ng/mL (32.4% vs. 14.6%, p = 0.013). A PCT value of >0.09 ng/mL could predict major complications (defined as open conversion, mechanical ventilation, and death). Conclusions: Current evidence is plagued by the heterogeneity of small sample studies. Though PCT has some role in assessing severity and predicting difficult cholecystectomy, and postoperative complications in AC patients, more evidence is necessary to validate its use.

Vitamin D supplementation for irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is a prevalent and complex gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits. Observational studies have suggested a relationship between serum vitamin D levels and IBS symptoms. This systematic review and meta-analysis aimed to investigate the clinical effects of vitamin D supplementation on IBS symptom severity and quality of life (QoL) measures. METHODS: Medline, Embase, Scopus, Web of Science, and The Cochrane Library databases were systematically searched. Data abstraction and quality assessment were conducted by four authors independently, and discrepancies were resolved through consensus from the senior author. Continuous data were pooled with standardized mean difference (SMD) using the DerSimonian and Laird's random-effects model. Sensitivity analysis by risk of bias and potentially "predatory" publication were performed as well. RESULTS: A total of 685 patients across eight studies were included in the meta-analysis. Vitamin D supplementation significantly improved IBS symptom severity scale scores, with a SMD of -0.77 (95% confidence interval [CI] -1.47 to -0.07, P = 0.04, I2  = 91%). Improvements in IBS-QoL scores were also observed, albeit not statistically significant (SMD 0.54; 95% CI -0.34 to 1.41, P = 0.15, I2  = 87%). However, small sample sizes, a relatively young study population, limited ethnicities, and varied vitamin D dosing strategies across the studies were notable limitations. CONCLUSIONS: Vitamin D supplementation could be part of our clinical armamentarium when managing IBS patients due to the potential efficacy and good safety profile. Further randomized, controlled trials are required to confirm the therapeutic effects.

A scoping review of qualitative studies on pre-hospital analgesia administration and practice.

BACKGROUND: Pain is an exceedingly common complaint in the pre-hospital setting. Despite advancements in organizational protocols and guidelines, many emergency medical services (EMS) systems still fail to provide optimal pain management. This scoping review thus aimed to map the body of qualitative literature pertaining to factors influencing pre-hospital analgesia administration and practice in order to clarify concepts and understanding as well as to identify any knowledge gaps. METHODS: The review protocol was guided by the framework outlined by Arksey and O'Malley and ensuing recommendations made by Levac and colleagues. Five databases were searched from inception till October 26, 2021, namely MEDLINE, EMBASE, CINAHL, The Cochrane Library, and Scopus. The search strategy was developed in consultation with a medical information specialist. A total of 5848 records were screened by abstract and title by four independent researchers. 199 records were included for full text review. From these, 15 articles were eligible for thematic analysis based on pre-defined inclusion criteria. RESULTS: Included studies found that practitioner, patient, and environmental factors influenced the administration and practice of pre-hospital analgesia. Key barriers included the difficulty in assessing pain, poor inter-professional relationship, knowledge deficits, stress and anxiety, and miscellaneous factors, such as concerns over drug-seeking behaviours. Some possible solutions were proposed, and pre-hospital EMS systems and healthcare institutions could consider bridging some of these gaps. There was a notable paucity of Asian studies, and a variety of EMS settings with different protocols and workflows were examined, hence systemic factors including guidelines and legislations cannot and should not be generalized across every healthcare system. CONCLUSION: The factors influencing pre-hospital analgesia administration and practice remain incompletely understood. Existing tools and practice guidelines were also inadequate. This scoping review provided an overarching perspective of the extant literature, highlighting some of the significant barriers, enablers, and areas for further research.

Actin network disassembly powers dissemination of Listeria monocytogenes.

Several bacterial pathogens hijack the actin assembly machinery and display intracellular motility in the cytosol of infected cells. At the cell cortex, intracellular motility leads to bacterial dissemination through formation of plasma membrane protrusions that resolve into vacuoles in adjacent cells. Here, we uncover a crucial role for actin network disassembly in dissemination of Listeria monocytogenes. We found that defects in the disassembly machinery decreased the rate of actin tail turnover but did not affect the velocity of the bacteria in the cytosol. By contrast, defects in the disassembly machinery had a dramatic impact on bacterial dissemination. Our results suggest a model of L. monocytogenes dissemination in which the disassembly machinery, through local recycling of the actin network in protrusions, fuels continuous actin assembly at the bacterial pole and concurrently exhausts cytoskeleton components from the network distal to the bacterium, which enables membrane apposition and resolution of protrusions into vacuoles.

Scoping review of the second victim syndrome among surgeons: Understanding the impact, responses, and support systems.

BACKGROUND: It is thought that 50% of healthcare providers experience Second Victim Syndrome (SVS) in the course of their practice. The manifestations of SVS varies between individuals, with potential long-lasting emotional effects that impact both the personal lives and professional clinical practice of affected persons. Although surgeons are known to face challenging and high-stress situations in their profession, which can increase their vulnerability to SVS, majority of studies and reviews have focused squarely on nonsurgical physicians. METHODS: This scoping review aimed to consolidate existing studies pertaining to a surgeon's experience with SVS, by broadly examining the prevalence and impact, identifying the types of responses, and evaluating factors that could influence these responses. The scoping review protocol was guided by the framework outlined by Arksey and O'Malley and ensuing recommendations made by Levac and colleagues. Three databases (MEDLINE, EMBASE and Cochrane Library) were searched from inception till March 19, 2023. RESULTS: A total of 13 articles were eligible for thematic analysis based on pre-defined inclusion criteria. Effects of SVS were categorized into Psychological, Physical and Professional impacts, of which Psychological and Professional impacts were particularly significant. Factors affecting the response were categorized into complication type, surgeon factors and support systems. CONCLUSION: SVS adds immense psychological, emotional and physical burden to the individual surgeon. There are key personal, interpersonal and environmental factors that can mitigate or exacerbate the effects of SVS, and greater emphasis needs to be placed on improving availability and access to services to help surgeons at risk of SVS.

The risk of stroke and post-stroke mortality in people with schizophrenia: A systematic review and meta-analysis study.

Sources of heterogeneity in risk of stroke and mortality risk following acute-stroke in schizophrenia are understudied. We systematically searched four electronic-databases until 1-November-2022, and conducted meta-analysis to synthesize estimates of stroke-risk and post-stroke mortality for schizophrenia patients relative to non-schizophrenia counterparts. Subgroup-analyses and meta-regression models stratified by sex, nature of sample (incident/prevalent), geographical region, study-period and time-frame following stroke were conducted when applicable. Fifteen and 5 studies were included for meta-analysis of stroke-risk (n=18,368,253; 129,095 schizophrenia patients) and all-cause post-stroke mortality (n=289,231; 4,477 schizophrenia patients), respectively. Schizophrenia patients exhibited elevated stroke-risk (relative-risk =1.55[95% CI:1.31-1.84]) relative to non-schizophrenia controls. Schizophrenia was associated with increased stroke-risk in both sexes, study-periods of 1990s and 2000s, and irrespective of nature of sample and geographical regions. Meta-regression revealed regional differences in relative-risk for stroke, but limited by small number of studies. After removal of an outlier study, meta-analysis demonstrated that schizophrenia was associated with increased overall (hazard-ratio=1.37[1.30-1.44]), short-term (≤90 days; 1.29[1.14-1.46]) and longer-term (≥1 year; 1.45[1.32-1.60]) post-stroke mortality rates. Raised post-stroke mortality rate for schizophrenia was observed irrespective of nature of sample, geographical regions and study-periods. Taken together, schizophrenia is associated with increased stroke-risk and post-stroke mortality. Multilevel-interventions are required to reduce these physical-health disparities.

What Has Longitudinal 'Omics' Studies Taught Us about Irritable Bowel Syndrome? A Systematic Review.

Irritable bowel syndrome is a prototypical disorder of the brain-gut-microbiome axis, although the underlying pathogenesis and mechanisms remain incompletely understood. With the recent advances in 'omics' technologies, studies have attempted to uncover IBS-specific variations in the host-microbiome profile and function. However, no biomarker has been identified to date. Given the high inter-individual and day-to-day variability of the gut microbiota, and a lack of agreement across the large number of microbiome studies, this review focused on omics studies that had sampling at more than one time point. A systematic literature search was performed using various combinations of the search terms "Irritable Bowel Syndrome" and "Omics" in the Medline, EMBASE, and Cochrane Library up to 1 December 2022. A total of 16 original studies were reviewed. These multi-omics studies have implicated Bacteroides, Faecalibacterium prausnitzii, Ruminococcus spp., and Bifidobacteria in IBS and treatment response, found altered metabolite profiles in serum, faecal, or urinary samples taken from IBS patients compared to the healthy controls, and revealed enrichment in the immune and inflammation-related pathways. They also demonstrated the possible therapeutic mechanisms of diet interventions, for example, synbiotics and low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol (FODMAP) diets on microbial metabolites. However, there was significant heterogeneity among the studies and no uniform characteristics of IBS-related gut microbiota. There is a need to further study these putative mechanisms and also ensure that they can be translated to therapeutic benefits for patients with IBS.

Local Therapy on Clinically Lymph Node-positive Prostate Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Patients with clinically lymph node-positive (cN1) prostate cancer (PCa) are traditionally regarded to have metastatic disease, and the role of local therapy (LT) in their treatment remains unclear. OBJECTIVE: To evaluate the outcomes of cN1 PCa patients treated with LT, and secondarily to compare between different modalities of LT, including radiotherapy (RT) and radical prostatectomy (RP). EVIDENCE ACQUISITION: A bibliographic search was performed using Medline, Embase, and the Cochrane Library to identify studies comparing the survival outcomes of cN1 PCa patients treated with LT (RT or RP) with those who did not receive any form of LT (observation or androgen deprivation therapy alone). The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations were followed. Survival outcomes of the addition of LT were assessed using a random-effect model. EVIDENCE SYNTHESIS: A total of 8522 patients across eight studies were included. LT significantly improved overall survival (OS) across all time points from 2 to 10 yr compared with patients without LT, most notably providing a durable benefit in 10-yr OS (odds ratio [OR]: 1.49, 95% confidence interval [CI] 1.06-2.10). Both RT and RP were associated with benefits to both OS and recurrence-free survival, with no significant difference in OS between both modalities in medium-term follow-up (4-yr OR: 0.76, 95% CI 0.41-1.40, p = 0.19). CONCLUSIONS: Regardless of modality, the use of LT in cN1 patients improved OS. Future studies should aim to identify patients who could benefit from LT and include more comprehensive survival data including biochemical recurrence. PATIENT SUMMARY: In this study, we evaluated the outcomes of clinically lymph node-positive (cN1) prostate cancer (PCa) patients treated with local therapy (LT) and compared between different modalities of LT, including radiotherapy (RT) and radical prostatectomy (RP). We found that the addition of LT for cN1 PCa patients leads to a significant improvement in survival outcomes, most notably for overall survival, with no significant difference between RT and RP.

Three-dimensional tomographic imaging and characterization of iron compounds within Alzheimer's plaque core material.

Although it has been known for over 50 years that abnormal concentrations of iron are associated with virtually all neurodegenerative diseases, including Alzheimer's disease, its origin, nature and role have remained a mystery. Here, we use high-resolution transmission electron microscopy (HR-TEM), energy dispersive X-ray (EDX) spectroscopy and electron energy-loss spectroscopy (EELS), electron tomography, and electron diffraction to image and characterize iron-rich plaque core material - a hallmark of Alzheimer's disease pathology - in three dimensions. In these cores, we unequivocally identify biogenic magnetite and/or maghemite as the dominant iron compound. Our results provide an indication that abnormal iron biomineralization processes are likely occurring within the plaque or the surrounding diseased tissue and may play a role in aberrant peptide aggregation. The size distribution of the magnetite cores implies formation from a ferritin precursor, implicating a malfunction of the primary iron storage protein in the brain.

RNAi screen reveals host cell kinases specifically involved in Listeria monocytogenes spread from cell to cell.

Intracellular bacterial pathogens, such as Listeria monocytogenes and Rickettsia conorii display actin-based motility in the cytosol of infected cells and spread from cell to cell through the formation of membrane protrusions at the cell cortex. Whereas the mechanisms supporting cytosolic actin-based motility are fairly well understood, it is unclear whether specific host factors may be required for supporting the formation and resolution of membrane protrusions. To address this gap in knowledge, we have developed high-throughput fluorescence microscopy and computer-assisted image analysis procedures to quantify pathogen spread in human epithelial cells. We used the approach to screen a siRNA library covering the human kinome and identified 7 candidate kinases whose depletion led to severe spreading defects in cells infected with L. monocytogenes. We conducted systematic validation procedures with redundant silencing reagents and confirmed the involvement of the serine/threonine kinases, CSNK1A1 and CSNK2B. We conducted secondary assays showing that, in contrast with the situation observed in CSNK2B-depleted cells, L. monocytogenes formed wild-type cytosolic tails and displayed wild-type actin-based motility in the cytosol of CSNK1A1-depleted cells. Furthermore, we developed a protrusion formation assay and showed that the spreading defect observed in CSNK1A1-depleted cells correlated with the formation of protrusion that did not resolve into double-membrane vacuoles. Moreover, we developed sending and receiving cell-specific RNAi procedures and showed that CSNK1A was required in the sending cells, but was dispensable in the receiving cells, for protrusion resolution. Finally, we showed that the observed defects were specific to Listeria monocytogenes, as Rickettsia conorii displayed wild-type cell-to-cell spread in CSNK1A1- and CSNK2B-depleted cells. We conclude that, in addition to the specific host factors supporting cytosolic actin-based motility, such as CSNK2B, Listeria monocytogenes requires specific host factors, such as CSNK1A1 in order to form productive membrane protrusions and spread from cell to cell.

Regulatory mimicry in Listeria monocytogenes actin-based motility.

The actin-based motility of the intracellular pathogen Listeria monocytogenes relies on ActA, a bacterial factor with a structural domain allowing it to mimic the actin nucleation-promoting activity of host cell proteins of the WASP/WAVE family. Here, we used an RNAi-based genetic approach in combination with computer-assisted image analysis to investigate the role of host factors in L. monocytogenes cell-to-cell spread. We showed that the host cell serine/threonine kinase CK2 is required for efficient actin tail formation by L. monocytogenes. Furthermore, CK2-mediated phosphorylation of ActA regulated its affinity for the actin-nucleating ARP2/3 complex, as is the case for CK2-mediated phosphorylation of WASP and WAVE. Thus, ActA not only displays structural mimicry of WASP/WAVE family members, but also regulatory mimicry, having precisely co-opted the host machinery regulating these proteins. Comparisons based on ActA amino acid sequence suggest that unrelated pathogens that display actin-based motility may have evolved a similar strategy of regulatory mimicry.